Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins

With the aim of increasing therapeutic indexes of novel cyclic depsinonapep tide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C ' 3. It is rather encouraging to note that several members o f the newly synthesized prodrugs described herein (e.g., 2a, 2e, and 4e) ex hibited comparable in vivo efficacy to that achieved by the parent compound s, yet free of tail vein irritation and histamine induced toxicity in vivo.